Biomedical subjects
Publications and source records attributed to S Hamilton.
We report a case of nonfunction of an anatomically normal kidney associated with a contralateral hypernephroma. X-ray and radionuclide imaging suggested a disturbance of the contralateral renal blood flow at the microvascular level. Normal function resumed after tumor resection. The implications for management are discussed.
Decreased local obstetric care appears to be increasing the rate of premature births to rural populations. With increased numbers of premature and complicated births in rural populations, understanding the impact of the Neonatal Intensive Care Unit (NICU) environment on the development of parent-child relationships becomes critical. NICU infants appear to be at increased risk for failure to thrive, child abuse, and neglect. Some reports suggest that the frequency of parental visits to the NICU can predict infants likely to be at risk. Because rural parents visiting infants hospitalized in urban centers are likely to visit less often, understanding this possible relationship is critical. In this controlled prospective study, three groups of parents were observed visiting their hospitalized infants: (1) those visiting "in house" while the mother was still hospitalized; (2) those whose visits required one hour or less in travel time; and (3) those whose visits required more than one hour in travel time. Results showed that travel time influenced the frequency of visits, with fewer visits from those living furthest from the NICU. However, those visiting from greater distances stayed with their infants longer so that there was no difference in the total visiting time over a two-week period. Direct observations of the visits by both mothers and fathers showed no differences in the content of parent-child interactions among groups. Thus, visit frequency alone must be viewed cautiously as a potential indicator of failure to bond with a hospitalized infant, especially in settings serving rural populations.
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Coordinate loss of one copy of the p53 gene and mutation of the remaining copy occur in colorectal carcinomas and in many other human malignancies. However, the prevalence of p53 gene mutations in carcinomas which maintain both parental copies of p53 has not previously been evaluated. Moreover, it is not known whether p53 gene mutations are limited to malignant tumors or whether they can also occur in benign neoplasms. To answer these questions, a total of 58 colorectal tumors have been examined; in each tumor, allelic losses were assessed using restriction fragment length polymorphisms and p53 gene mutations were assessed by sequencing cloned polymerase chain reaction products. The following conclusions emerged: (a) p53 gene mutations occurred but were relatively rare in adenomas, regardless of size and whether the adenomas were derived from patients with familial adenomatous polyposis; (b) In carcinomas as well as in adenomas, p53 gene mutations were infrequently observed in tumors which contain both copies of chromosome 17p (17% of 30 tumors), while tumors which lost one copy of chromosome 17p usually had a mutation in the remaining p53 allele (86% of 28 tumors); (c) p53 gene mutations were found at similar frequencies in primary tumor samples and in cell lines derived from tumors. These and other data suggest that the rate limiting step in p53 inactivation is point mutation and that once a mutation occurs, loss of the remaining wild-type allele rapidly follows. Both mutations and allelic losses generally occur near the transition from benign to malignant growth, and the p53 gene may play a causal role in this progression.
The biological effects of cytotoxic macrolide polyethers, the bistratenes, isolated from the ascidian Lissoclinum bistratum, have been examined. Bistratene A was toxic to HL-60 human promyelocytic leukemia cells with an IC50 value of 424 nM. At lower concentrations (10-100 nM), bistratene A induced the incomplete differentiation of these cells along the monocyte/macrophage pathway. These effects were not due to inhibition of DNA synthesis. Bistratene B had similar effects to bistratene A. At micromolar concentrations these compounds enhance the phospholipid-dependent activity of type II protein kinase C from bovine spleen. The bistratenes provide new probes for studying the molecular mechanisms governing cell growth and differentiation.
Minicholecystostomy was performed in 24 elderly patients, under local anaesthesia. All had symptomatic gallstones removed utilizing endoscopy and fluoroscopy. These procedures were well tolerated, with no significant complications, despite severe coexistent disease. One patient has had recurrent problems due to gallstones and one has died from disseminated malignancy. The remaining 22 are well and symptom-free. This combined surgical and radiological approach is a useful alternative procedure for patients with gallstones who are a poor risk for general anaesthesia.
Dictyostelium discoideum glycoproteins contain mannose-6-SO4 in highly immunogenic N-linked oligosaccharides. To more precisely define the structural requirements of the antigenic determinant, we have analyzed the oligosaccharides synthesized by two mutant strains (HL241 and HL243) that lack it. Both mutant strains synthesize N-linked oligosaccharides which are very similar to each other but are smaller and less charged than those derived from the wild-type. Both mutants contain substantial amounts of Man-6-SO4, and only a single residue of Man-6-P-OCH3 per chain, in contrast to the wild-type which may have 1 or 2 such residues. Neutral species are similar to the wild-type in that they can still be modified by the addition of residues of fucose and N-acetylglucosamine. Both mutant strains synthesize a truncated lipid-linked oligosaccharide, Man6GlcNAc2, with the most probable structure being: (sequence; see text) based on Jack bean alpha-mannosidase, alpha-1,2-specific mannosidase digestions and methylation analysis. The presence of this small oligosaccharide appears to result from the loss of the mannosyltransferase(s) needed to synthesize structures larger than Man6GlcNAc2 and not from the absence of dolichol phosphate or dolichol-P-mannose synthetase. These data along with the analysis of another mutant strain suggest that the expression of the antigenic determinant requires a specific arrangement of Man-6-SO4 on the alpha-1,6 branch of the oligosaccharide linked to the beta-mannose.
An extended hamstring V-Y myocutaneous advancement flap is described that may be used to cover unusually large defects in the ischial region. Technical points that allow a large amount of flap advancement are discussed. Because of its large size, the flap can be raised and used on repeated occasions to repair defects from recurrent ischial pressure sores. Two patients are presented in whom the same flap was used repeatedly on multiple occasions, demonstrating the potential for preservation of future options in such patients when this flap is used.
The double-opposing-tab flap, a new method of nipple reconstruction used in 50 patients to date, is described. This technique uses two dermal-fat flaps, each similar to those described by Hartrampf, but with tab extensions inspired by the skate flap of Little. The donor sites of the two flaps are closed like Burrough's triangles, bringing the flaps into opposition so that they support each other's projection. The tabs cover all the exposed fat on the nipple so that no skin graft is required on the nipple proper. The result is a nicely shaped nipple that can be designed directly over a scar, maintains a projection averaging 3.8 mm at 10 months, and is technically easy to construct.
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With the resurgence of oral cholecystography for assessing gallbladder function prior to new treatment methods, it is important to be aware of the possibility of gastro-duodenal retention of contrast medium, and its implications. Six patients who had retained Telepaque in the stomach or duodenum at oral cholecystography are described here. In each patient there was underlying pathology, including gastritis, peptic ulceration and neoplasm. The presence of retained contrast medium in the stomach or duodenum is a useful indication of disease in these areas.
The kinetics of activation of protein kinase C by oleic acid have been reinvestigated, using highly purified preparations of the rat brain and bovine spleen enzymes. Activation of both enzymes by oleic acid is enhanced dramatically by diolein, contrary to previous reports. In the presence of 9.7 microM diolein, the concentrations of oleic acid required for half-maximal activation are 5 microM and 9 microM for the rat brain and bovine spleen enzymes respectively, indicating that the system is much more sensitive to activation by fatty acids than previously recognized. Both enzymes also exhibit a pronounced lag in the activation at low concentrations of oleic acid. The kinetics of activation are very similar to those reported by Hannun et al. (J. Biol. Chem 260, 10039-10043), who characterized the activation of the rat brain enzyme by mixed micelles containing Triton X-100, phosphatidylserine and diolein.
Specific, high affinity sulfonylurea receptors were characterized on membranes of an insulin-secreting hamster beta cell line (HIT cells). Saturable binding of the sulfonylurea, [3H]glyburide, was linear up to 0.8 mg/ml membrane protein. Scatchard analysis of equilibrium binding data at room temperature indicated the presence of a single class of saturable, high affinity binding sites with a Kd of 0.76 +/- 0.04 nM and a Bmax of 1.09 +/- 0.13 pmol/mg protein, n = 9. The insulin secretory potency of glyburide, glipizide, tolbutamide, tolazamide, and carboxytolbutamide was compared to the ability of these ligands to displace [3H]glyburide from the sulfonylurea receptor. Tolbutamide, tolazamide, and glipizide demonstrated reasonable agreement with ED50 values of 15 microM, 3 microM, and 30 nM and Ki values of 25.3 microM, 7.2 microM, and 45 nM, respectively. The inactive tolbutamide metabolite, carboxytolbutamide, at the highest concentration tested, only partially displaced [3H]glyburide from the receptor and was a very poor secretagogue. At 37 degrees C the affinity of [3H]glyburide binding, Kd = 2.0 nM, was similar to the ED50 of 5.5 nM when the free glyburide concentrations were corrected for binding of the drug to albumin. These studies suggest that sulfonylureas initiate their biologic effect through a high affinity, specific interaction with sulfonylurea receptors on the beta cell membrane.
1. CNS serotonergic neurotransmission has been implicated in the control of appetitive behavior. The ratio of plasma tryptophan (TRP) to other large neutral amino acids (LNAA) is believed to regulate CNS serotonin (5-HT) synthesis. 2. After an overnight fast, plasma TRP ratios were determined in 23 normal weight bulimics and 7 normal controls. 3. All subjects were assessed for mood disorder using a SADS interview and Beck Depression ratings. 4. There was no significant difference in TRP ratios between bulimics and normal controls. TRP ratios in depressed bulimics were not significantly different from those of nondepressed bulimics. 5. Potential abnormalities in CNS serotonergic function in bulimics are not reflected in decreased baseline TRP ratios. Further investigation of the dynamic serotonergic system may prove fruitful. 6. Reduced availability of tryptophan for conversion to serotonin is not likely to be the postulated biological abnormality common to both depression and bulimia.
Male and female coping behaviors were compared in order to test the theory that men use instrumental coping strategies more frequently than women, who are thought to use emotion-focused coping solutions. We interviewed 51 female and 39 male first-year undergraduates by telephone three times a week for 8 weeks, using an inventory developed for 28 chronic stressors. Analyses of variance were used to test gender differences in frequency of daily stressors, concomitant perceptions of stress, and utilization of problem-solving behaviors. The majority of analyses showed no gender differences. The implications of these findings are discussed in light of cultural expectations.
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A 32-year old woman was found at surgery to have an esophageal leiomyoma arising within an epiphrenic diverticulum. These uncommon conditions may rarely occur together, causing difficulty in diagnosis of the leiomyoma. Other neoplasms may also arise in an epiphrenic diverticulum and should be borne in mind in this situation.